Retinoic acid (Vitamin A acid) is a substance which has an extremely important physiological effect on life-support functions, such as differentiating developing immature cells into mature cells that have a characteristic function and facilitating cell growth. Clinically, it has been found that retinoic acid is useful in treatment of Vitamin A deficiency, keratosis of epithelial tissue, leukemia, and certain types of cancers. It has been found that various Vitamin A derivatives which have been synthesized hitherto also have similar biological activity, and those compounds which have retinoic acid-like biological activity, including retinoic acid, are called retinoids.
However, in cases where a retinoid is used as a therapeutic drug, the retinoid is accumulated in the body due to its high lipid solubility and as a result, there have been a risk of developing retinoic acid syndrome. Further, the intrinsic toxicity of retinoic acid, such as skin irritation and teratogenicity, is also problematic.
Tamibarotene, a type of retinoid, has already been marketed as tablets; however, presently, no coating process is applied in order to maintain a favorable oral absorptivity.
Tamibarotene has at least two crystal polymorphs, and type 1 crystal (Patent Document 1) which melts at 193° C. and type 2 crystal (Patent Documents 2 and 3) which melts at 233° C. are known.
However, the type 1 crystal has problems in that it is extremely difficult to prepare a uniform crystal since transitions between crystal forms readily occur with a physical impact, so that it is unsuitable as the raw material for mass preparation of a pharmaceutical product which has a uniform standard. On the other hand, it is known that the type 2 crystal has a high stability not only for a physical impact, but also for heat, temperature, light and the like.
Further, in conventional tablet techniques including the manufacturing technique according to Patent Document 3, since the oral absorptivity is emphasized, a sufficient attention has not presently been paid to chemical hazard.    Patent Document 1: Japanese Patent No. 3001632    Patent Document 2: Japanese Unexamined Patent Application Publication No. S 61-76440    Patent Document 3: WO 2002/018322